Extended release of bioactive factors to treat refractory wounds Chronic wounds significantly decrease quality of life, lead to severe disability, and are huge burdens on healthcare and caregivers. Diabetes mellitus is expected to afflict 366 million people worldwide by 2030. Among these patients, approximately 15% will develop diabetic foot ulcers. Underlying chronic wounds, abnormal cell phenotypes and chronic inflammation inhibit normal healing processes and elevate the risk of infection. Current clinical solutions are expensive, time-consuming, largely unsuccessful, and lack patient self-management. The overarching goal of this translational study is to advance nursing science and the wound care field, by healing chronic wounds with one-time administration of sustained, local release of growth factors. This effective and economical treatment will be achieved using a new vehicle that protects the bioactivity of the protein cargo. Growth factor signaling plays a pivotal role in the natural wound healing process. The major limitation in growth factor therapies has been the lack of an appropriate delivery system to provide for prolonged signaling. Controlled delivery of growth factor will reduce patient morbidity and risk of infection in chronic wounds while helping patients to manage their care more autonomously. This research focuses on testing the efficacy of a delivery system we recently designed for wound-implicated growth factors and has three specific aims: Aim 1. Investigate the effects of HB-EGF coacervate on wound healing in vitro using normal and diabetic primary human dermal cells and evaluate the safety of the coacervate treatment. Aim 2. Evaluate the efficacy of controlled delivery of HB-EGF to improve diabetic wound healing in a polygenic type 2 diabetic mouse model. Aim 3. Investigate the controlled delivery of HB-EGF to accelerate diabetic wound healing in a porcine model. This proposal will provide the foundation for an easy-to-use product that significantly improve healing of wounds, increase patient self-reliance and quality of life, and reduce the interruption and loss of productivity patients currently must accept. Therefore, this new technology would enable not only improved health outcomes, but also more self-management for individuals with chronic wounds.